miR15a and miR16 in Chilean type 1 diabetes patients: possible association with apoptosis, inflammatory, or autoimmunity markers.

AIM: Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by the progressive destruction of ß cells, mediated by the interaction between T cells and several cytokines. The pathogenesis of T1D has established its possible relationship with miRNAs. In this study, we analyze the expression profile of miR-15a and miR-16 in peripheral blood mononuclear cells (PBMCs) and their possible association with apoptosis, inflammation, or autoimmunity markers. PATIENTS AND METHODOLOGY: 38 T1D patients and 41 control subjects were recruited. mRNAs were analyzed by means of qPCR and TaqMan probes. PBMCs were treated with different concentrations of glucose (baseline, 11 and 25 mM) with or without an inflammatory stimulus as TNF-α (10 ng/ml). RESULTS: A decrease in the levels of the miR-15a expression in basal conditions is observed in T1D patients compared to healthy control subjects (relative units 0.5 vs. 1.8, p < 0.05). This change in miR-15a and miR-16 is not affected by the addition of TNF-α. No association is observed with inflammatory markers (IL-6, TNF-α, vCAM) or apoptosis (bcl2 expression). The relationship with immunological markers shows an interaction effect between miR16 and IA-2 (p < 0.03). CONCLUSION: TNF-α does not affect the expression profile of miR-15a and miR16 in PBMCs. A weak correlation is observed between miR-16 and with the autoimmunity profile (IA-2 autoantibody).

miR15a and miR16 in Chilean type 1 diabetes patients: possible association with apoptosis, inflammatory, or autoimmunity markers.

AIM: Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by the progressive destruction of ß cells, mediated by the interaction between T cells and several cytokines. The pathogenesis of T1D has established its possible relationship with miRNAs. In this study, we analyze the expression profile of miR-15a and miR-16 in peripheral blood mononuclear cells (PBMCs) and their possible association with apoptosis, inflammation, or autoimmunity markers. PATIENTS AND METHODOLOGY: 38 T1D patients and 41 control subjects were recruited. mRNAs were analyzed by means of qPCR and TaqMan probes. PBMCs were treated with different concentrations of glucose (baseline, 11 and 25 mM) with or without an inflammatory stimulus as TNF-α (10 ng/ml). RESULTS: A decrease in the levels of the miR-15a expression in basal conditions is observed in T1D patients compared to healthy control subjects (relative units 0.5 vs. 1.8, p < 0.05). This change in miR-15a and miR-16 is not affected by the addition of TNF-α. No association is observed with inflammatory markers (IL-6, TNF-α, vCAM) or apoptosis (bcl2 expression). The relationship with immunological markers shows an interaction effect between miR16 and IA-2 (p < 0.03). CONCLUSION: TNF-α does not affect the expression profile of miR-15a and miR16 in PBMCs. A weak correlation is observed between miR-16 and with the autoimmunity profile (IA-2 autoantibody).

C-Reactive protein and insulin growth factor 1 serum levels during the menstrual cycle in adolescents with Type 1 diabetes.

AIMS: To evaluate C-reactive protein, insulin growth factor 1 and lipid levels during the follicular and luteal phases in adolescents with Type 1 diabetes. METHODS: Adolescents with Type 1 diabetes (N = 40) and healthy controls (C; N = 43) were studied during the follicular and luteal phases of their menstrual cycles. C-Reactive protein, insulin growth factor 1 and lipid levels were measured. RESULTS: Adolescents with Type 1 diabetes exhibited higher C-reactive protein levels than the C group during the follicular (P < 0.0001) and luteal phases (P < 0.01). The elevation of C-reactive protein levels was more pronounced in overweight adolescents with Type 1 diabetes than in adolescents in the C group. More adolescents with Type 1 diabetes were classified as having an elevated risk of cardiovascular disease (C-reactive protein > 3 mg/l) in the luteal phase than in the follicular phase (37.5% and 17.5%, respectively); half of the overweight adolescents with Type 1 diabetes in the luteal phase reached this level. BMI was the only significant factor affecting follicular and luteal phase C-reactive protein levels in adolescents with Type 1 diabetes. Lower insulin growth factor 1 levels were observed during both phases of the menstrual cycle in adolescents with Type 1 diabetes compared with controls. An elevation in insulin growth factor 1 levels in the luteal phase relative to the follicular phase was observed in controls, but not in adolescents with Type 1 diabetes. Luteal insulin growth factor 1 and C-reactive protein exhibited an inverse correlation (r = -0.4, P = 0.01). CONCLUSIONS: Adolescents with Type 1 diabetes have higher C-reactive protein levels and lower insulin growth factor 1 levels relative to controls, especially during the luteal phase. Type 1 diabetes diminishes the natural elevation in insulin growth factor 1 levels observed during the luteal phase in controls. Excess weight exacerbates the subclinical inflammatory state observed during both phases of the menstrual cycle in adolescents with Type 1 diabetes.

Lack of association between the fatty acid binding protein 2 (FABP2) polymorphism with obesity and insulin resistance in two aboriginal populations from Chile.

The aim of this study was to assess the frequency of fatty acid binding protein 2 (FABP2) Ala54Thr genetic polymorphism and to evaluate its association with obesity and insulin resistance in Chilean aboriginal populations. A sample of 96 urban Aymara and 111 urban Mapuche subjects aged 20-80 years were recruited for this cross-sectional study. Glucose, insulin and lipid profile were measured in fasting plasma samples. Insulin resistance was estimated through the HOMA-IR model. FABP2 Ala54Thr genotypes were determined by PCR followed by RFLP analysis. The allele frequency of Thr54 variant was estimated as 18.2% in Aymara subjects, which is one of the lowest reported to date. The corresponding frequency in Mapuche subjects was 31.9% (p<0.002). Regarding genotype-phenotype associations, no significant differences were found in any of the anthropometric or metabolic variables according to Ala54Thr genotypes. After adjustment by BMI and metabolic variables through a logistic regression analysis, the association of the FABP2 polymorphism with ethnic group persisted (Mapuche group: OR=2.37, 95% CI 1.319-4.277, p=0.004) It is unlikely that Ala54Thr polymorphism of the FABP2 gene plays a relevant role in obesity and insulin resistance in Chilean ethnic groups.

Genetic predisposition and environmental factors leading to the development of insulin-dependent diabetes mellitus in Chilean children.

This study was designed to examine the hypothesis that some environmental factors increase the risk for insulin-dependent diabetes mellitus. Data on dietary history was collected from 80 diabetic children from the Santiago de Chile Registry and from 85 nondiabetic control subjects who were comparable in terms of age, sex, and ethnic characteristics. Early exposure was defined as the ingestion of food sources other than maternal milk before 3 months of age. To define genetic susceptibility to insulin-dependent diabetes mellitus each subject was typed in terms of HLA DQA1 and DQB1, and the possible conformation of susceptible heterodimers was considered as a risk marker. Fewer children were exclusively breast fed in the diabetic group than in the control group (21.55 +/- 15.05 vs 33.95 +/- 20.40 weeks, P<0.01). In addition, exposure to cow's milk and solid foods occurred earlier in the diabetic group than in the control group (15.90 +/- 10.95 vs 21.15 13.65 and 16.85 +/- 10.25 vs 21.20 +/- 12.35 weeks, P<0.05). Our data show that a short duration of breast-feeding and early exposure to cow's milk and solid foods may be important factors in the development of insulin-dependent diabetes mellitus. The high relative risk observed in individuals genetically predisposed indicates an interaction effect between genetic and environmental components.

Genetic differences in HLA-DQA1* and DQB1* allelic distributions between celiac and control children in Santiago, Chile.

Celiac disease is a permanent gluten intolerance strongly associated with HLA class II antigens. The over presentation of particular HLA alleles and haplotypes has been described in several populations. Different lines of evidence obtained during the last years suggest that a particular HLA-DQ heterodimer, encoded by the DQA1*0501 and DQB1*0201 genes in cis or trans conformation, confers the primary disease susceptibility. We report the HLA class II allelic distribution and DQA1/ DQB1 genotypes in 62 Chilean celiac patients compared with 124 control subjects in Santiago, Chile. We found a pronounced increase of the "susceptible" alleles :DQA1*0501 (0.480 vs 0.169, Pc < 0.0005), DQB1*0302 (0.430 vs 0.242, Pc = 0.002) and DQB1*0201 (0.250 vs 0.125, Pc = 0.037) in celiac patients in comparison with control children. As for "protective" alleles, we detected a high frequency of DQA1*0101 (0.310 vs 0.160, Pc = 0.01), DQA1*0201 (0.105 vs 0.010, Pc < 0.0075) and DQB1*0301 (0.250 vs 0.100, Pc = 0.010) in controls. In relation to risk haplotypes, the main combination observed was the conformation DQ8 (DQB1*0302/DQA1*0301) over DQ2 (DQB1*0201/DQA1*0501). In conclusion, results show that celiac disease in Chilean patients is primarily associated with DQ8 conformation. This is concordant with the high frequency of DR4 alleles (in linkage disequilibrium with DQB1*0302) detected in Amerind groups in Chile, where DQB1*0302 is more frequent than DQB1*0201.

Transmission of high-risk HLA-DQB1 alleles in Chilean type 1 diabetic patients and their parents: stratification by the presence of ICA or GAD65 autoantibodies.

AIM: The purpose of this study was to assess whether the transmission of DQB1*0201 and DQB1*0302 alleles from heterozygous parents to Chilean type 1 diabetic patients depends on the presence of antibodies such as glutamic acid decarboxilase (GAD65) or Islet Cell (ICA) autoantibodies in the affected case. MATERIAL AND METHODS: A study of incident type 1 diabetic cases and parents was carried out in Santiago, Chile during 1997-98. The use of the case-parental design eliminates the possibility that case-controls differences are due to selection of controls whose genetic backgrounds differ systematically from those of cases. HLA-DQB1 polymorphisms were determined in cases and parents from n = 83 families using polymerase chain reaction and oligonucleotide dot-blot analysis. Detection of GAD65 antibodies was performed using a simple radio-binding asssay. Conventional ICA were detected by indirect immunofluorescence. RESULTS: Transmission disequilibrium test indicate a strong association between DQB1*0201 and DQB1*0302 and type I diabetes. When comparing the two subsets of families defined by having an affected child tested negative or positive for GAD65 antibodies (39 and 44 case-parent trios respectively) the probability of transmission of DQB1*0201 significantly differed between such strata (p-value=0.025). The pattern of transmission of DQB1*201 allele was also significantly different in the two subsets of families defined by ICA-or ICA+ cases (23 and 60 trios respectively) (p-value = 0.028). No differences were found in the transmission of DQB1*0302 allele in the different strata defined by the autoimmunity status of the proband. CONCLUSION: Our results reveal that DQB1*0201 allele may display distinct associations with type I diabetes depending on the autoimmunity to ICA and GAD65 autoantibodies.

Applicability of the case-parent design in the etiological research of Type 1 diabetes in Chile and other genetically mixed populations.

In case-control studies, spurious associations between Human Leukocyte Antigen (HLA) alleles and Type 1 diabetes could arise as a result of population stratification, if there are ethnic differences between cases and non-related controls. The Chilean population has several unique features which make it ideal for the study of the effect of stratification by ethnicity on genetic epidemiological research. The incidence rates of Type 1 diabetes in Chilean Aboriginal populations are very low compared to Caucasian populations, while the frequency of the alleles in HLA loci also vary across ethnic groups. In order to avoid the confounding effect of ethnicity, one possible remedy would be the use of cases and their parents in place of non-related controls. The case-parent design offers an adequate framework for the study of the association between HLA polymorphisms and Type 1 diabetes in the Chilean population and can also be applicable to other genetically mixed populations especially in the Americas.

HLA-DR, DQ and anti-GAD antibodies in first degree relatives of type I diabetes mellitus.

The differential antibody response to glutamic acid decarboxylase (anti-GAD) and to islet cell cytoplasm (ICA) according to HLA-DR and DQ genotypes were examined in 28 Spanish patients with Type I diabetes mellitus (11.1 +/- 10.4 year diabetes duration) and their 41 first degree non-diabetic relatives. Anti-GAD was detected by radioimmunoprecipitation and ICA by indirect immunofluorescence and HLA-DR/DQ alleles were assigned by PCR and sequence specific oligonucleotide probes. The frequency in patients of positivity for ICA was 7.1% and of anti-GAD+ 64.3%, and in relatives, the frequency of ICA+ was 4.9%, and anti-GAD+ 9.8%. Concurrent positivity for ICA and anti-GAD existed in only one patient, and in none of the relatives. We confirm for a Spanish population the high frequency of risk genotypes for Type I, involving DR3, DR4 and DQB1*0302 (DQ8) which were present in 26 of 28 (93%) patients and 32 of 41 (78%) relatives. The most frequent genotypes were DR3/DQB1*0201/DQA1*0501-DR4/DQB1*0302/DQA1*0301( 9 patients, 32%; 6 relatives, 15%), DR3/DQB1*0201/ DQA1*0501-DR3/DQB1*0201/DQA1*0501 (5 patients, 18%; 7 relatives, 17%) and DE3/DQB1*0201/DQA1*0501-DR1/ DQB1*0501/DQA1*0101(5 patients, 18%; 1 relative, 2%). Positivity for anti-GAD or for ICA did not correlate with gender, or age at onset or duration of DM. The distribution of high risk HLA genotypes were similar regardless the anti-GAD or anti-ICA status either in patients or in their relatives.

One of the lowest validated incidence rates of insulin dependent diabetes mellitus in the Americas: Santiago, Chile.

The goal of this study was to estimate the average annual incidence rate of insulin-dependent diabetes mellitus (IDDM) in Santiago as part of a Multinational Project in Childhood Diabetes (Diabetes Mondiale or DiaMond). Incidence was calculated among subjects under 15 years of age, through a retrospective search and confirmation method from 1 January 1986 to 31 December 1992. Hospitals and private offices of endocrinologists and specialists in diabetes were surveyed. A total of 252 registered cases, 118 boys and 134 girls, for an annual incidences of 2.36/100,000 hab.year. which is one of the lowest validated rates in the Americas.

Prevalence of type 2 diabetes and obesity in rural Mapuche population from Chile.

The aim of this study was to estimate the prevalence of Type 2 diabetes, impaired glucose tolerance (IGT), and obesity in the Mapuche natives from rural areas in Chile. This cross-sectional study involved men (n = 95) and women (n = 224) older than 20 y from an aboriginal ethnic group (Mapuches), residing in rural communities from the south of Chile. Prevalence of Type 2 diabetes and IGT was calculated according to the World Health Organization criteria. Data on age, degree of ancestral purity, obesity, and hypertension were also obtained. The prevalence of Type 2 diabetes in rural Mapuche natives was estimated as 3.2% (95% CI: 0.7--9.0) in men and 4.5% (95% CI: 2.2--8.1) in women. The overall prevalence of obesity was 56.1% (95% CI: 50.5--61.6): 40.0% (95% CI: 30.1--40.8) in men and 62.9% (95% CI: 56.3--69.3) in women (P value < 0.001). These data suggest that the prevalence of obesity and Type 2 diabetes has been increasing during recent years in the Mapuche communities. The prevalence estimated in this study is higher than that reported 15 y ago. This suggests an important role of lifestyle changes as a possible explanation for epidemiologic transition.

Low prevalence of type 2 diabetes despite a high average body mass index in the Aymara natives from Chile.

The aim of this study was to estimate the prevalence of type 2 diabetes mellitus (DM2), impaired glucose tolerance (IGT), and the frequency of dyslipidemia, obesity, and hypertension in the rural Aymara population from Northern Chile. In this cross-sectional study, 196 Aymara adult subjects were characterized with respect to their reported physical activity, fasting plasma glucose levels, insulin concentrations, blood pressures, body mass indexes, and plasma lipid profiles. The participants also underwent a 2-h oral glucose tolerance test. The diagnostic criteria for DM2 and IGT followed those of the World Health Organization. The overall prevalence of DM2 was estimated as 1.5% (95% confidence interval: 0.3--4.5). Overall prevalence of IGT was calculated as 3.6% (1.5--7.3). The occurrence of obesity and dyslipidemia was relatively high in the Aymara population, although the frequency of sedentary habits, and the prevalence of hypertension were low. In conclusion, the prevalence of DM2 in the rural Aymara population living at high altitudes in Northern Chile, was much lower than that of other Amerindian groups that adopted lifestyles from industrialized Western societies. Despite a relatively high prevalence of a body mass index of at least 30 kg/m(2), especially in women (23.5%), high physical activity levels and low plasma-insulin concentrations may have been responsible in part for the low prevalence of DM2 in the Aymara population.

Anthropometric measurements in the elderly population of Santiago, Chile.

OBJECTIVE: There are few studies on anthropometry and nutritional status in large and representative samples of elderly populations in Chile and South America. We describe age and sex differences in weight, height, body mass index, knee height, waist circumference, midarm circumference, triceps skinfold thickness, arm muscle area, and calf circumference in Chilean elderly subjects. METHODS: This was a population-based, cross-sectional study. A total of 1220 elderly persons (819 women and 411 men; age range, 60-99 y) were recruited in the city of Santiago (Chile) through a probabilistic sampling procedure carried out from October to December 1999. RESULTS: Men were significantly heavier and taller than women in all age groups, whereas body mass index values were significantly higher in women than in men. All anthropometric variables showed a decrease in average values with aging in men and women. The apparent negative slopes for the decline in average values of body weight with aging was of greater magnitude in women than in men (-0.42 kg/y and -0.54 kg/y in male and female subjects, respectively). However, significant age x sex interaction was detected only for triceps skinfold thickness. In women, quadratic terms for age provided a significantly better fit than did the simple linear model for the association between age and weight, body mass index, waist circumference, triceps skinfold thickness, calf circumference, or midarm circumference. CONCLUSION: These observations indicated that body weight changes associated with aging might be more severe in Chilean women than in men, probably determining a differential pattern of lean and fat mass loss.

[Relationship between leptin and insulin sensitivity in patients with polycystic ovary syndrome]. / Relación entre leptina y sensibilidad a la insulina en mujeres con síndrome de ovario poliquístico.

BACKGROUND: The relationship between leptin and insulin sensitivity, sexual steroids and insulin concentrations in women with polycystic ovary syndrome is still controversial. The objective of this study was to assess the relationship between insulin levels, insulin resistance parameters and serum leptin concentrations in healthy and polycystic ovary syndrome women. PATIENTS AND METHODS: 33 hyperandrogenic polycystic ovary syndrome women (GHA) and 27 healthy women (GS) were included in this study. Leptin, insulin, sex-hormone binding globulin (SHBG), testosterone and estradiol concentrations were determined in a basal sample. Body mass index, waist diameter and waist to hip ratio were recorded. Insulin sensitivity was calculated by means of insulin tolerance test and glycemia/insulinemia ratio. RESULTS: The leptin concentration was not different between GHA and GS. Insulin levels and free testosterona index (FTI) were higher in GHA than GS (p < 0.01). The glycemia/insulinemia ratio, SHBG levels, and insulin sensitivity were lower in GHA (p < 0.01). In both groups positive correlations between leptin concentration and body mass index (p < 0.01), waist diameter (p < 0.01), insulin levels (p < 0.01) and glycemia/insulinemia ratio (p < 0.01) were observed. Only GHA showed correlation between insulin sensitivity and leptin concentration (p < 0.02). SHBG and leptin levels were not correlated. CONCLUSIONS: The leptin concentration was not different between GHA and healthy women, although they are metabolically different. This phenomenon could be due to the fact that in hyperandrogenic women the effects of insulin resistance and hyperandrogenemia counteract each other.

Incidence rate and spatio-temporal clustering of type 1 diabetes in Santiago, Chile, from 1997 to 1998.

OBJECTIVE: To estimate the incidence rate of type 1 diabetes in the urban area of Santiago, Chile, from March 21, 1997 to March 20, 1998, and to assess the spatio-temporal clustering of cases during that period. METHODS: All sixty-one incident cases were located temporally (day of diagnosis) and spatially (place of residence) in the area of study. Knox's method was used to assess spatio-temporal clustering of incident cases. RESULTS: The overall incidence rate of type 1 diabetes was 4.11 cases per 100,000 children aged less than 15 years per year (95% confidence interval: 3.06 - 5.14). The incidence rate seems to have increased since the last estimate of the incidence calculated for the years 1986 - 1992 in the metropolitan region of Santiago. Different combinations of space-time intervals have been evaluated to assess spatio-temporal clustering. The smallest p-value was found for the combination of critical distances of 750 meters and 60 days (uncorrected p-value = 0.048). CONCLUSIONS: Although these are preliminary results regarding space-time clustering in Santiago, exploratory analysis of the data method would suggest a possible aggregation of incident cases in space-time coordinates.

Adiposity and bone mineral density of Chilean elderly women in relation to toll-like receptor 4 gene polymorphisms.

BACKGROUND: It has been proposed that the toll-like receptor-4 gene (TLR4) may participate in the development of obesity and osteoporosis, in addition to its well-known role in the immune response. On the other hand, the adipose tissue of obese subjects shows an increased expression of the proinflammatory cytokine, tumour necrosis factor-alpha (TNF-alpha), which is released after lipopolysaccharide recognition by TLR4. AIM: To estimate the allele/genotype frequencies and linkage disequilibrium measures of Asp299Gly and Thr399Ile polymorphisms of the TLR4 gene in the Chilean elderly population, and to screen for their association with variables related to adiposity or bone mineral density. SUBJECTS AND METHODS: The study group included 227 unrelated Chilean elderly women (61-95 years) recruited from a population-based sample. Adiposity and bone mineral density measures were obtained using dual-energy X-ray absorptiometry. RESULTS: The allele frequencies for TNF -308A, TLR4 299Gly and TLR4 -399Ile were 9.3%, 4.6% and 4.4%, respectively, with Asp299Gly and Thr399Ile being in strong linkage disequilibrium (D' = 0.88). Although seriously restricted by the low frequency of the allele variants, no relevant association between genotypes and adiposity-related variables were found. Likewise, no significant association between osteoporosis status (categorized as osteoporosis, osteopenia or normal status) with TLR4 Asp299Gly or TNF -308G>A genotypes was found. CONCLUSION: It is unlikely that TLR4 Asp299Gly, TLR4 Thr399Ile or TNF -308G>A polymorphisms have a major influence on adiposity, bone mineral density or osteoporosis status in Chilean elderly women.

Increasing incidence of type 1 diabetes in population from Santiago of Chile: trends in a period of 18 years (1986-2003).

UNLABELLED: STUDY OBJECTIVE AND SETTING: The aim of this study is to determine the incidence rate of type 1 diabetes in the metropolitan region of Santiago, Chile from 1 January 1986 to 31 December 2003. DESIGN: Population-based incidence study. PARTICIPANTS: A case must fulfill the following requirements to be included in this study: age at onset: 0 to 14 years, diagnosed with diabetes and placed on insulin, diagnosed within the defined time period, and to be a resident of the metropolitan region of Santiago at the time of the diagnosis. The population 'at risk' is the population less than 15 years of age. RESULT: The overall rate of type 1 diabetes was estimated as 4.02 cases per 100 000 children per year (95% confidence interval: 2.98-4.83). CONCLUSION: The incidence of type 1 diabetes in Santiago, Chile has increased during the last years. This data are concordant with the observation that the incidence of type 1 diabetes is increasing in Latin America and worldwide.

Incidence rate of type 1 diabetes in Santiago (Chile) by HLA-DQA1 and DQB1 genotypes.

The aim of this study was to estimate annual incidence rate of type 1 diabetes according to the levels of genetic susceptibility provided by HLA-DQA1 and HLA-DQB1 genotypes. Two information sources were used: (1) a population-based incidence study in which 61 incident cases were ascertained during 1 year in Santiago, Chile (incidence rate: 4.11 cases per 100,000 children per year) and (2) a case-control comparison of 57 cases (recruited from the incidence study) and 125 controls. Susceptibility alleles were defined as DQA1*0301 and DQA1*0501 for DQA1 gene and alleles DQB1*0201 and DQB1*0302 for DQB1 gene. In DQA1 gene, the highest point estimate of the incidence rate was calculated for the genotype DQA1*0501/DQA1*0501 (33.04 cases per 100,000 children aged less than 15 years old and per year; 95% CI: 9.22-118.33). In the DQB1 gene, the highest risk was estimated for the genotype DQB1*0201/DQB1*0201 (20.35 cases per 100,000 children aged less than 15 years old and per year; 95% CI: 5.26-78.67). This study shows an application on how a transformation of the logistic equation based on Bayes' theorem can be used to estimate incidence rates from case-control studies and population-based incidence rates.

Plasma leptin and insulin levels in Aymara natives from Chile.

The purpose of this study was to examine the relationship of plasma leptin levels with respect to obesity, gender, age and insulin levels in the native Aymara population. The Aymara natives live at high altitudes in isolated regions in the north of Chile, and they maintain distinctive genetic and cultural characteristics. Plasma leptin and insulin levels were correlated with body mass index (BMI), sex and age in a sample of 147 adult Aymara subjects who participated in a cross-sectional study. Multivariate analysis showed significant differences in leptin levels (dependent variable: natural log of leptin) by gender (p < 0.0001), and by BMI (p < 0.001), without significant statistical interaction between gender and BMI. The effect of age achieved statistical significance in the multivariate analysis (p = 0.02). Gender, BMI and insulin are independently associated with plasma leptin levels. On the other hand, the multivariate analysis of the plasma insulin concentration (dependent variable: natural log of insulin levels) shows that insulin is strongly associated with BMI (p < 0.0001), although non-statistically significant differences of insulin levels by sex (p = 0.07) or age (p = 0.9) were detected at alpha 0.05 level. Thus, in the special ecosystem where the Aymara population live, a strong and independent association between sex, obesity and insulin levels with plasma leptin levels has been detected.

Associations between HLA-DQB1 high-risk alleles and type I diabetes do not depend on cytomegalovirus antibody status at onset: a case-parent study conducted in Chile.

The purpose of the present study is to ascertain whether the associations between HLA-DQB1*0201 and DQB1*0302 alleles and childhood diabetes depend on the presence of antibodies to human cytomegalovirus (CMV). A study of incident type I diabetes cases and parents was conducted in Santiago, Chile. HLA-DQB1 polymorphisms were determined in 85 case-parent trios (255 subjects), while the detection of CMV was carried out only in the incident cases. As expected, HLA-DQB1 polymorphisms are strongly associated with type I diabetes, with crude odds ratios of 3.7 (95% confidence interval (CI) 1.8-7.7) for the DQB1*0201 allele and 10.3 (95% CI 5.0-21.4) for the DQB1*0302 allele. In the subset of families with CMV+ cases, the odds ratios were estimated as 3.7 (95% CI 1.6-8.6) for the DQB1*0201 allele and 11.1 (95% CI 4.8-25.8) for the DQB1*0302 allele. In families with patients who tested negative for CMV antibodies, the odds ratios were calculated as 3.5 (95% CI 0.7-16.8) for the DQB1*0201 allele, and 8.0 (95% CI 1.8-34.7) for the DQB1*0302 allele. There was no evidence of statistical interaction between CMV antibodies and the DQB1*0201 allele (P value = 0.9) or the DQB1*0302 allele (P value = 0.7). In conclusion, alleles DQB1*0302 and DQB1*0201 do not display distinct associations with type I diabetes depending on the presence of antibodies for CMV.